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EBIO Does Not Induce Cardiomyogenesis in Human Pluripotent Stem Cells but Modulates Cardiac Subtype Enrichment by Lineage-Selective Survival
Subtype-specific human cardiomyocytes (CMs) are valuable for basic and applied research. Induction of cardiomyogenesis and enrichment of nodal-like CMs was described for mouse pluripotent stem cells (mPSCs) in response to 1-ethyl-2-benzimidazolinone (EBIO), a chemical modulator of small-/intermediat...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5311470/ https://www.ncbi.nlm.nih.gov/pubmed/28089668 http://dx.doi.org/10.1016/j.stemcr.2016.12.012 |
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author | Jara-Avaca, Monica Kempf, Henning Rückert, Michael Robles-Diaz, Diana Franke, Annika de la Roche, Jeanne Fischer, Martin Malan, Daniela Sasse, Philipp Solodenko, Wladimir Dräger, Gerald Kirschning, Andreas Martin, Ulrich Zweigerdt, Robert |
author_facet | Jara-Avaca, Monica Kempf, Henning Rückert, Michael Robles-Diaz, Diana Franke, Annika de la Roche, Jeanne Fischer, Martin Malan, Daniela Sasse, Philipp Solodenko, Wladimir Dräger, Gerald Kirschning, Andreas Martin, Ulrich Zweigerdt, Robert |
author_sort | Jara-Avaca, Monica |
collection | PubMed |
description | Subtype-specific human cardiomyocytes (CMs) are valuable for basic and applied research. Induction of cardiomyogenesis and enrichment of nodal-like CMs was described for mouse pluripotent stem cells (mPSCs) in response to 1-ethyl-2-benzimidazolinone (EBIO), a chemical modulator of small-/intermediate-conductance Ca(2+)-activated potassium channels (SKs 1–4). Investigating EBIO in human pluripotent stem cells (PSCs), we have applied three independent differentiation protocols of low to high cardiomyogenic efficiency. Equivalent to mPSCs, timed EBIO supplementation during hPSC differentiation resulted in dose-dependent enrichment of up to 80% CMs, including an increase in nodal- and atrial-like phenotypes. However, our study revealed extensive EBIO-triggered cell loss favoring cardiac progenitor preservation and, subsequently, CMs with shortened action potentials. Proliferative cells were generally more sensitive to EBIO, presumably via an SK-independent mechanism. Together, EBIO did not promote cardiogenic differentiation of PSCs, opposing previous findings, but triggered lineage-selective survival at a cardiac progenitor stage, which we propose as a pharmacological strategy to modulate CM subtype composition. |
format | Online Article Text |
id | pubmed-5311470 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-53114702017-02-22 EBIO Does Not Induce Cardiomyogenesis in Human Pluripotent Stem Cells but Modulates Cardiac Subtype Enrichment by Lineage-Selective Survival Jara-Avaca, Monica Kempf, Henning Rückert, Michael Robles-Diaz, Diana Franke, Annika de la Roche, Jeanne Fischer, Martin Malan, Daniela Sasse, Philipp Solodenko, Wladimir Dräger, Gerald Kirschning, Andreas Martin, Ulrich Zweigerdt, Robert Stem Cell Reports Article Subtype-specific human cardiomyocytes (CMs) are valuable for basic and applied research. Induction of cardiomyogenesis and enrichment of nodal-like CMs was described for mouse pluripotent stem cells (mPSCs) in response to 1-ethyl-2-benzimidazolinone (EBIO), a chemical modulator of small-/intermediate-conductance Ca(2+)-activated potassium channels (SKs 1–4). Investigating EBIO in human pluripotent stem cells (PSCs), we have applied three independent differentiation protocols of low to high cardiomyogenic efficiency. Equivalent to mPSCs, timed EBIO supplementation during hPSC differentiation resulted in dose-dependent enrichment of up to 80% CMs, including an increase in nodal- and atrial-like phenotypes. However, our study revealed extensive EBIO-triggered cell loss favoring cardiac progenitor preservation and, subsequently, CMs with shortened action potentials. Proliferative cells were generally more sensitive to EBIO, presumably via an SK-independent mechanism. Together, EBIO did not promote cardiogenic differentiation of PSCs, opposing previous findings, but triggered lineage-selective survival at a cardiac progenitor stage, which we propose as a pharmacological strategy to modulate CM subtype composition. Elsevier 2017-01-12 /pmc/articles/PMC5311470/ /pubmed/28089668 http://dx.doi.org/10.1016/j.stemcr.2016.12.012 Text en © 2017 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Article Jara-Avaca, Monica Kempf, Henning Rückert, Michael Robles-Diaz, Diana Franke, Annika de la Roche, Jeanne Fischer, Martin Malan, Daniela Sasse, Philipp Solodenko, Wladimir Dräger, Gerald Kirschning, Andreas Martin, Ulrich Zweigerdt, Robert EBIO Does Not Induce Cardiomyogenesis in Human Pluripotent Stem Cells but Modulates Cardiac Subtype Enrichment by Lineage-Selective Survival |
title | EBIO Does Not Induce Cardiomyogenesis in Human Pluripotent Stem Cells but Modulates Cardiac Subtype Enrichment by Lineage-Selective Survival |
title_full | EBIO Does Not Induce Cardiomyogenesis in Human Pluripotent Stem Cells but Modulates Cardiac Subtype Enrichment by Lineage-Selective Survival |
title_fullStr | EBIO Does Not Induce Cardiomyogenesis in Human Pluripotent Stem Cells but Modulates Cardiac Subtype Enrichment by Lineage-Selective Survival |
title_full_unstemmed | EBIO Does Not Induce Cardiomyogenesis in Human Pluripotent Stem Cells but Modulates Cardiac Subtype Enrichment by Lineage-Selective Survival |
title_short | EBIO Does Not Induce Cardiomyogenesis in Human Pluripotent Stem Cells but Modulates Cardiac Subtype Enrichment by Lineage-Selective Survival |
title_sort | ebio does not induce cardiomyogenesis in human pluripotent stem cells but modulates cardiac subtype enrichment by lineage-selective survival |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5311470/ https://www.ncbi.nlm.nih.gov/pubmed/28089668 http://dx.doi.org/10.1016/j.stemcr.2016.12.012 |
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